H. Emori et al., PROSPECTIVE VALIDATION OF HIGH-SHEAR WET GRANULATION PROCESS BY WET GRANULE SIEVING METHOD .2. UTILITY OF WET GRANULE SIEVING METHOD, Drug development and industrial pharmacy, 23(2), 1997, pp. 203-215
The general utility of a method for determination of high-shear wet gr
anulation end point by monitoring the wet granule particle size distri
bution was evaluated. Wet granulation was conducted in a 25-liter high
-shear mixer using four model drugs with different solubilities and pa
rticle sizes (ethenzamide, unmilled and milled acetaminophen, and anti
pyrine). For each drug formulation, its wet granule particle size frac
tion and target range for granulation end point determination were sel
ected based on the tablet characteristics that are known to be influen
ced by the wet granulation process. Granules manufactured under differ
ent conditions (i.e., different main and chopper blade speeds and bind
er supplying rate) but manufactured to the same granulation end point
determined by the selected fraction and range showed very similar gran
ule characteristics and subsequently very similar tablet characteristi
cs. From the fact that there was a good correlation between the wet an
d dry-sized granule particle size distributions even if the drying met
hod was changed from fluid-bed drying to vacuum drying, the general ap
plication of the end point determining method was verified. Further, t
he method was shown to be sensitive to the critical granulation parame
ters for granulation progression and to be very capable of determining
the granulation extent. Thus, it was suggested that the method is app
licable to various drugs and formulations for determination of wet gra
nulation end point.